ototoxicity after high-dose chemotherapy with cyclophosphamide, thiotepa and carboplatin followed by stem cell transplantation in patients with breast cancer

Our purpose was to determine the risk of ototoxicity in breast cancer patients receiving a myeloablative regimen consisting of cyclophosphamide 6000 mg/m², thiotepa 500mg/m² and carboplatin 800mg/m² (CTCb) followed by stem cell transplantation. Fourteen consecutive patients with breast cancer were treated with high dose chemotherapy consisting of the CTCb regimen followed by stem cell transplantation. A pretransplant complete hearing study was obtained which consisted of hearing case history, audiometry and tympanometry. In addition, DPOAE (Distortion Product Otoaccoustic Emissions) was done to evaluate measurable changes in the cochlear (outer hair cell) functioning. Pre-transplant, all patients had no clinical evidence of hearing impairment and hearing studies were normal. Eleven patients had hearing studies and a telephone interview posttransplant. One patient was lost to follow-up and two patients died. One of the 11 patients tested had an abnormal post-transplant hearing study but none of them had clinically detectable hearing impairment. In our prospective study of breast cancer patients treated with the CTCb regimen, we did not observe clinically detectable hearing impairment in any of the patients tested.     

Elimination of acute myelogenous leukemic cells from marrow and tumor suspensions in the rat with 4-hydroperoxycyclophosphamide

Cell suspensions of normal rat marrow mixed with rat acute myelogenous leukemic cells were prepared and incubated in vitro with graded doses of 4-hydroperoxycyclophosphamide (4HC). The cell suspensions were injected into rats prepared with a lethal dose of total body irradiation. Animals injected with these cells survived fatal irradiation induced aplasia. In a dose related manner 4HC was able to "purge" tumor cells from the cell mixtures. Thus, animals given cell suspensions incubated with the lower doses of 4HC showed prolonged survival before death from leukemia and animals given cell suspensions incubated with higher doses of 4HC survival lethal irradiation without the subsequent appearance of leukemia. These studies clearly establish that tumor cells may be eliminated from normal marrow suspensions without completely destroying the pluripotent stem cells.     

原发性肝癌临床病理学新趋势

原发性肝癌（简称肝癌）临床病理学研究发展迅速，尤其是日本．自２０世纪６０年代开始建立了日本肝癌研究会，每２ａ汇总日本全国医院临床病理学资料．１组织分类汇总日本研究会报道的肝癌患者３７９６２例，其中１６０３８例（４２３％）经病理证实．在病理诊断中，１...     

Chromosomal abnormalities identify high-risk and low-risk patients with acute lymphoblastic leukemia

The importance of banded chromosome analyses in predicting long-term outcome in acute lymphoblastic leukemia (ALL) was evaluated in this follow-up study of 329 patients from the Third International Workshop on Chromosomes in Leukemia. Patients were divided into ten groups according to pretreatment karyotype: no abnormalities, one of the following structural abnormalities [the Philadelphia chromosome, translocations involving 8q24,t(4;11), 14q+, 6q-] or, in the remaining cases, modal number [less than 46, 46, 47 to 50, greater than 50]. Achievement and duration of complete remission (CR) and survival differed among chromosome groups (P less than .0001). Karyotype was an independent prognostic factor for duration of first CR and survival, even when age, initial leukocyte count (WBC), French-American-British (FAB) type, and immunologic phenotype were considered. Among adults, prolonged remission and survival were uncommon in all chromosome groups. Only in the normal karyotype group was median survival even two years. Among children, striking differences in long-term remission and survival were seen depending upon karyotype. Children in the greater than 50 group did best, with 70% remaining in first CR for a median duration in excess of five years. Children in the 47-50, 6q-, and normal karyotype groups also had prolonged survivals. In contrast, certain translocations [t(9;22)(q34;q11), t(4;11)(q21;q14-23), t(8;14)(q24;q32)] identified children who had short survivals, even in the presence of favorable prognostic factors including a low WBC, L1 morphology, and non-T, non-B immunologic phenotype. We conclude that chromosome analysis is required at diagnosis in patients with ALL, and that children with these specific translocations should be managed as having high-risk ALL.     

Enhanced external counterpulsation for ischemic heart disease: what's behind the curtain?

Enhanced external counterpulsation (EECP) has been shown to reduce angina and to improve objective measures of myocardial ischemia in patients with refractory angina. Prospective clinical studies and large treatment registries suggest that a course of EECP is associated with prolongation of the time to exercise-induced ST-segment depression and resolution of myocardial perfusion defects, as well as with enhanced exercise tolerance and quality of life. With a growing knowledge base supporting the safety and beneficial clinical effects associated with EECP, this therapy can be considered a valuable treatment option, particularly in patients who have exhausted traditional revascularization methods and yet remain symptomatic despite optimal medical care. However, although the concept of external counterpulsation was introduced almost four decades ago, and despite growing evidence supporting the clinical benefit and safety of this therapeutic modality, little is firmly established regarding the mechanisms responsible for the beneficial effects associated with this technique. Suggested mechanisms contributing to the clinical benefit of EECP include improvement in endothelial function, promotion of coronary collateralization, enhancement of ventricular function, peripheral effects similar to those observed with regular physical exercise, and nonspecific placebo effects. This review summarizes the current evidence for a contribution of these mechanisms to the clinical benefit associated with EECP.     

Amino acid sequence of a platelet-binding human anti-DNA monoclonal autoantibody

The complete amino acid sequences of the variable regions of the heavy and light chains of a human IgM monoclonal platelet-binding autoantibody have been determined. This antibody, HF2-1/17, produced by a human x human hybridoma prepared from lymphocytes of a patient with systemic lupus erythematosus and thrombocytopenia, is polyreactive with single-stranded DNA, synthetic polynucleotides, sulfated carbohydrates, and acidic glycolipids isolated from platelet membranes. The heavy chain is of the VHIII subgroup, and the light chain is of the VKI subgroup. The heavy chain is the expression product of the VH26 germline gene. The light chain bears significant homology to other immunoglobulins of known primary structure, including WEA, GAL, HAU, HK101, and DEE. These results suggest that HF2-1/17 may be an autoantibody derived with little or no modification from germline genes. A model of the antibody combining site suggests that arginine 24 and arginine 30 in the light chain (CDR1) interact with a surface defined by phosphate or sulfate groups of the antigen.     

Ontogeny of B-lymphocyte function. III. In vivo and in vitro studies on the ease of tolerance induction in B lymphocytes from fetal, neonatal, and adult mice

The ease of tolerance induction in B lymphocytes from fetal, neonatal, and adult mice was studied in vivo, in a cell transfer system, and in vitro. Three different tolerogens were used: ultracentrifuged BGG, DNP(6)-D-GL, and ultracentrifuged DNP(22)-BGG. Irradiated thymectomized mice were reconstituted with B cells from fetal or neonatal liver or adult spleen or bone marrow. The mice were injected with tolerogen 1 day later. They were given normal thymus cells and challenged with either BGG or DNP(44)-BGG between 4 and 14 days after tolerance induction. With BGG no difference in ease of B-cell tolerance induction was observed in mice reconstituted with B cells from 17-day fetal liver, neonatal liver, 8- day-old spleen, adult spleen, or adult bone marrow. B cells from 14-day fetal donors are relatively resistant to tolerance induction. In contrast, with DNP(6)-D-GL and DNP(22)-BGG B cells from neonatal donors were clearly more susceptible to tolerance induction than were B cells from adult donors. Comparable results were obtained in studies on tolerance induction in vitro. Neonatal B cells were more susceptible than adult B cells to tolerance induction upon culture with DNP(6)-D-GL or DNP(22)-BGG. However, neonatal and adult B cells were identical with respect to ease of tolerance induction in vitro with deaggregated BGG. The results suggest that there are multiple mechanisms for B-cell tolerance induction. Immature B cells appear to be more susceptible to tolerance induction by some mechanisms but not by others. It is suggested that immature B cells are more susceptible to tolerance induction with moderately polyvalent antigens such as hapten-carrier conjugates. With antigens like BGG which do not haverepeated epitopes no difference between mature and fetal B cells in regard to ease of tolerance induction is observed. These observations raise questions about the importance of relative ease of tolerance induction in immature B cells as a mechanism controlling the normal induction of self tolerance.     

‘GAP’ in radiotherapy services in Australia and New Zealand in 2009

Aim: In this study we estimated (a) the number of linear accelerators required in Australia and New Zealand to achieve a 52.3% treatment rate; (b) the ‘GAP’ between the actual and required number of linear accelerators; c) the number of persons not treated (PNT), premature deaths (PD) and years of life lost (YLL) as a result of the ‘GAP’; and (d) to review the actions being taken by health jurisdictions in Australia and in New Zealand to address the ‘GAP’ and reach the 52.3% treatment rate. Material and Methods: The actual number of fully staffed and operating linear accelerators (A) in Australian and New Zealand was obtained from a survey of radiotherapy facilities in December 2009. The required number of linear accelerators (R) was calculated from the projected cancer incidence figures for 2009 and was based on 1.6 linear accelerators being required per 1000 new cancer patients. The ‘GAP’ in Radiotherapy services (G) was R minus A. The maximum treatment capacity (MTC) was the ratio of A over R multiplied by 52.3%, assuming that all linear accelerators were operating at 100% capacity. As each linear accelerator can treat 331 new patients each year, the number of new cancer PNT is G × 331. The estimated 5-year survival benefit from radiotherapy is 16%, and the average survival for all patients receiving radiotherapy (radical and palliative) is 0.76 year. Hence, the number of PD attributed to the ‘GAP’ is PNT × 16%, and the YLL to cancer is PNT × 0.76. A literature search and local knowledge of health department Radiotherapy Plans in all jurisdictions were used to determine the action being taken to achieve a 52.3% treatment rate. Results: In 2009, the ‘GAP’ was 50 linear accelerators in Australia and the MTC was 38%, the same as it was in 1999, but there has been an increase in PNT each year from 7419 in 1999 to 16 550 in 2009, and PD each year increased from 1187 in 1999 to 2649 in 2009, and YLL each year increased from 5638 in 1999 to 12 585 in 2009. In New Zealand in 2009, the ‘GAP’ was nine linear accelerators and the MTC was 38%. An estimated 3310 persons did not receive radiotherapy in 2009 in New Zealand, and as a result, there were 523 PD and 2266 YLL. The review showed that new and replacement machines were being installed in all jurisdictions in Australia and in New Zealand. Only Victoria and Queensland have a Radiotherapy Plan beyond 2010, but both have underestimated the projected cancer incidence. Conclusion: Urgent action is needed by health departments and governments on both sides of the Tasman to improve access and equity to this essential cancer treatment. There is merit in the Baume Report recommendation of establishing a national body to oversee radiotherapy services in all jurisdictions in Australia. A similar central body should also be considered for New Zealand.     

游离足趾移植术中Ⅱ趾血供系统的特点

目的：游离足趾移植是拇指Ⅱ类以上缺损再造术的首选。分析与Ⅱ趾移植相关的足部供血系统的血管走行、分支情况及变异程度，并提出临床应用中为保证手术成功而采取的相应对策。方法：对1978—03/2007—06天津医院手、显微外科收治的91例Ⅱ趾移植再造拇（手）指患者进行回顾性分析，所有病例均为ⅡB-ⅢB类型拇指缺损，均为择期手术，对治疗方案知情同意。术中遇第一跖背动脉纤细型，采取足背动脉-足底深支-第一跖底动脉的第2套供血系统。当第一跖背动脉走行不定而误伤时，手术继续进行，完整切取Ⅱ趾后，进行第一跖背动脉吻合修复。注意第一跖背动脉至足趾的分支解剖特点，辨清与Ⅱ趾的关系，采取不同的手术对策。结果：91例拇指缺损患者获得了97．8％的成活率及优良的外形与功能恢复，移植术中Ⅱ趾的使用率是100％。Ⅱ趾的血供系统特点：①由足背动脉发出的第二跖背动脉很少见，足背动脉的弓状动脉分支也很少见。②第一跖背动脉起始、走行、口径虽不恒定，但是有章可循。③第一跖背动脉终末交通支及至Ⅱ趾的分支情况分为3型，各型对Ⅱ趾的血供也有其不同特点。结论：全面掌握与Ⅱ趾移植相关的足部供血系统的解剖特点，术中仔细游离并采取相应的处理方法，是保证手术成功的关键。